Patients with the acquired immune deficiency syndrome (AIDS) have developed an unprecedented number of disseminated infections caused by the opportunistic pathogens belonging to the Mycobacterium avium-intracellulare (MAI) complex. Effective control or eradication of these facultative intracellular organisms appears to depend largely on an intact cellular immune host response comprised of antigen-sensitized T lymphocytes, their secretory products (lymphokines), and lymphokine-activated tissue macrophages. Thus, it is not surprising that (a) MAI infections frequently develop in T cell deficient AIDS patients, and (b) that these patients typically fail to respond to conventional multi-drug therapy and often experience persistent high-grade bacillemia and widely disseminated and progressive infection until death. Characteristic autopsy findings include poor or absent inflammatory and granulomatous responses and visceral macrophages heavily parasitized with MAI--presumably reflecting grossly impaired lymphokine secretion and non-activated tissue macrophages. We have recently demonstrated that gamma interferon (IFN-Gamma) appears to be the key T cell lymphokine which activates the human monocyte-derived macrophage to exert antimicrobial activity against intracellular pathogens. In addition, we have shown that T cells from AIDs patients with opportunistic infections fail totally to secrete IFN-Gamma in response to stimulation with specific microbial antigen. These patients' monocyte-derived macrophages, however, are fully capable of responding in vitro to recombinant human IFN-Gamma with enhanced antimicrobial activity. This work forms the basis of this proposal in which we will determine the role and effect of IFN-Gamma in the immunopathogenesis and therapy of MAI infections in AIDS. Our aims are to (1) determine the conditions required to activate human macrophages to kill or inhibit intracellular MAI in vitro and define the role of IFN-Gamma in this antimycobacterial activity, (2) confirm that T cells from AIDs patients with MAI fail to secrete IFN-Gamma in response to specific stimulation with mycobacterial antigens, (3) develop an animal model of disseminated MAI infection with which to define in vivo both the role of IFN-Gamma in the host cellular immune response to MAI and the efficacy of treatment with IFN-Gamma, and (4) determine the effect of IFN-gamma as experimental replacement immunotherapy for AIDS patients with MAI infetions.